In general, the central nervous system (CNS) is well defended against infection. The spine and brain are sheathed in tough, protective membranes. The outermost membrane, the dura mater, and the next layer, the arachnoid, entirely encase the brain and spinal cord. However, these defenses are not absolute. In some cases, bacteria gain access to areas within the CNS. Bacterial infections can be pyogenic infections (e.g., meningitis; brain abscess; subdural and epidural abscesses), tuberculosis, neurosyphilis, or leprosy. Typically, bacterial invasion results from the spread of a nearby infection; for example, a chronic sinus or middle ear infection can extend beyond its initial site. Bacteria may also be conveyed to the CNS from distant sites of infection by the bloodstream. In rare cases, head trauma or surgical procedures may introduce bacteria directly into the CNS. However, the source of infection cannot always be identified.
The goal of treatment of a bacterial infection is to stop the infection, relieve symptoms, prevent complications, and, if necessary, provide life support. A two-pronged approach is taken to treat bacterial infections. First, antibiotic therapy against an array of potential infectious bacteria is begun. The second stage involves surgery to drain the infected site. Once the bacterial species is identified, drug therapy can be altered to a more specific antibiotic. However, surgery may not be an option in some cases, such as when there are numerous sites of infection or when infection is located in an inaccessible area of the brain.
Outer membrane protein A (OmpA) was initially described by Henning and coworkers in 1975. It has 325 amino acid residues and exhibits heat-modifiable electrophoretic mobility on SDS-PAGE. The N-terminal domain of OmpA is comprised of 177 amino acids and is believed to traverse the outer membrane eight times. OmpA is involved in maintaining the shape of bacteria, serves as a phage receptor and a receptor for F-mediated conjugation, and has limited pore-forming properties. OmpA enhances uptake of LPS into macrophages and has been reported to be involved in E. coli invasion of the central nervous system. WO 9201001 provides a method for producing pure cloned outer membrane proteins, and to provide a method for their renaturation so as to regain biologically or immunologically active epitopes which are capable of eliciting the production of antibodies in animals. Pascale Jeannin et al. reports that outer membrane protein A (OmpA) is a class of protein highly conserved among the Enterobacteriaceae family throughout evolution and OmpA appears as a new type of pathogen-associated molecular pattern (PAMP) usable as a vector in anti-infectious and therapeutic anti-tumor vaccines to elicit CTLs (Vaccine, Volume 20, Supplement 4, 19 Dec. 2002, pages A23-A27).
However, there are no reports relating to the new use of an outer membrane protein A and its derivatives in the treatment and/or prevention and/or diagnosis of bacterial infection in central nervous system and/or peripheral blood circulation.